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BB10005 > Chromosomes > Flashcards

Chromosomes Flashcards

1
Q

each chromosome

A

one linear strand of dna

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2
Q

Humans have how many

A

46

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3
Q

diploid

A

2n

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4
Q

Haploid

A

1n

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5
Q

Karyotype

A

number, size and shape of chromosomes eg XY and XX

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6
Q

The packing problem

A

each cell has 2m of dna in length

Fit into a nucleus of 6 um diameter

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7
Q

DNA packaging in chromosomes

A

Many levels of

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8
Q

Nucelosome

A

1st level of organisation in a chromosome
Bead on a string
Each nucleosome 147 bps wound 1.67 times per bead
Protein core made of histones
Between beads there is linker DNA with a H1 histone
Nucleosomes further coil up to form chromatin fibres

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9
Q

Histones

A

made up of 4 subunits which make up a tetramer
2 tetramers join together to make an octamer (bead)
Each octamer has 2 copies of each histone

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10
Q

nucleosomes are dynamic

A 
Chromatin remodelling factors:
Nucelosomes can be slid along the dna strand
Exchange histone octamers or subunits
Remove core histones
to expose DNA strand
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11
Q

HIstone tails

A

Can be modified by addition of chemical groups

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12
Q

Modification of histone tails

A

1-3 methyl groups added
acetyl groups
mostly on lysines

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13
Q

Methylation

A

chromatin condenses

gene repression

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14
Q

Acetylation

A

Chromatin decondenses

gene expression

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15
Q

Heterochromatin is self propagating

A

chromatin modification spreads along chromosomes

Methylated histone can recruit methyl transferases to modify neighbouring histones

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16
Q

Position effect

A

normally active gene silenced because of proximity to heterochromatin after dna breakage and re-joining

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17
Q

Other modification

A

serine phosphorylation
ubiquitination
SUMOlyation

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18
Q

What regulatory proteins bind to marked histones to ‘read the histone code’

A

chromatin remodelling complexes
transcription activators
Transcription repressors
DNA damage repair complexes

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19
Q

Epigenetics

A

modifications give rise to this

changes in the genome that are inherited but don’t involve changes in the DNA sequence

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20
Q

Epigenetic imprints passed on how

A
  • from mother to daughter cells
  • parent to child
  • passed along in tissues over course of life from: exposure to pollutants, stress, drugs
  • cancer: tumour supressors hypermethylated, leading to excessive cell division
21
Q

Where are methyl groups added to on DNA to repress transcription

A

sequences of dna that have lots of C-G repeats, known as CpG islands

22
Q

Dna methylation is essential for

A

normal development:

  • embryonic stem cells de-methylated mostly
  • occurs during differentiation
  • affected by diet, environment and ageing
23
Q

Functional links between histone methylation and dna methylation

A

Both give rise to gene silencing
Methylated histones can methylate the DNA and vice versa
Involves Histone 3, important for ‘maintenance methylation’

24
Q

Maintenance methylation

A

pattern of methylation needs to be maintained after dna is replicated on the new strands

25
Q

DNA packaging in chromosomes

A

Chromatin fibres loop and coil around each other on a protein scaffold
Assembled into loop regions. Loop regions not associated with a protein scaffold are available for transcription: euchromatin

Coiled again into heterochromatin

26
Q

LADs

A

lamina associated domains

27
Q

TADS

A

topologically associated domains
Sections of looped and coiled dna that are bundled together by cohesin
Boundaries formed by CTCF

28
Q

Cohesin

A

Protein complex that is a dimer that forms a ring structure

Wraps around DNA to induce loops

29
Q

CTCF

A

CCCTC- binding factor

TF expressed in all cell types

30
Q

Insulated neighbourhoods

A

The genes in these loops co-regulated

One or more per TAD

31
Q

Types of heterochromatin

A

Facultative and Constitutive

32
Q

Facultative heterochromatin

A

Potential for gene expression
Modification of histones or DNA
May switch between hetero and euchromatin states

33
Q

Constitutive heterochromatin

A

Condensed throughout cell cycle
Highly repetitive sequences
May play a role in chromatin structure
Telomeres and centromeres

34
Q

Telomeres

A

Long repetitive sequences of DNA on the ends of chromosomes
Protect the ends of DNA strands
Born with 11kb telomeres, when old 4kb telomeres

35
Q

Why do telomeres get shorter?

A

Dna repls enzymes can’t replicate very ends of dna strands so lose a little with every cell division
known as Hayflick limit

36
Q

Exception to telomeres getting shorter

A

If cells express telomerase

eg germ cells (eggs and sperm), embryonic stem cells, cancer cells

37
Q

Centromeres

A

Large arrays of repetitive dna
At junction of sister chromatids
Where microtubules attach during mitosis (kinetochore)

Instability of centromeres can result in mis-segregation of chromosomes:

  • embryonic death
  • cancer malignancy
38
Q

Chromosome replication and origins

A

multiple origins in repl

Each origin fires once per cycle- ensures DNA only copied once

39
Q

Replication timing

A

Eurochromatin repl early, start of S phase

Hetero later

40
Q

changes in chromosome structure

A

Various ways
Most common are deletions and substitutions- break in the chromosome and dna damage repair ligates and misses out a chunk of dna
Or during synthesis there could be synthesis of extra dna, which joins in a after breakage during rejoining
Or inversions- paracentric (away from the centromere) or pericentric (towards)
Or fusions- lose whole elements of the chromosome
Or translocation- sections of pair of chromosomes broken and rejoined- unbalanced/balanced

41
Q

TAD boundaries

A

fragile regions for chromosome breaks

42
Q

ALL

A

acute lymphoblastic leukaemia

43
Q

AML

A

Acute Myeloid Leukaemia

44
Q

AML and ALL

A

result from translocation between chromosome 9 and 22

Breakpoint Cluster Region in 22 is region that breaks

45
Q

What happens in AML and ALL

A

fusion of 2 genes
BCR- S/T kinase and Rho GEF
ABL1- tyrosine kinase (NES and NLS)

46
Q

BCR ABL fusion protein

A

constitutively active kinase (always on)
Means it is an oncogene
Leads to over-proliferation, stem- like state and resistance to cell death

47
Q

Chromosome changes in human evolution

A

We have 46, primates have 48
2 chromosomes involved in a telomere to telomere fusion evet to form our chromosome 2

Also
2 duplications of SRGAP2- resulted in expansion of neocortex (growth of grey matter)
Led to higher functions eg sensory perception, memory and language

48
Q

summary

A

dna wound around histones to form nucleosomes

BB10005 (27 decks)

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